Cystine/glutamate antiporter System x c - deficiency impairs insulin secretion in mice
de Baat A., Meier DT., Rachid L., Fontana A., Böni-Schnetzler M., Donath MY.
Animal Study, published in Diabetologia (2023) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Diabetologia (2023)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 37650924
- PMCID
- PMC10541846
- DOI
- 10.1007/s00125-023-05993-6
- Citations
- 16
Abstract (original English)
Aims/hypothesis Glutamate-induced cytotoxicity (excitotoxicity) has been detected in pancreatic beta cells. The cystine/glutamate antiporter System x c - exports glutamate to the extracellular space and is therefore implicated as driving excitotoxicity. As of yet, it has not been investigated whether System x c - contributes to pancreatic islet function. Methods This study describes the implications of deficiency of System x c - on glucose metabolism in both constitutive and myeloid cell-specific knockout mice using metabolic tests and diet-induced obesity. Pancreatic islets were isolated and analysed for beta cell function, glutathione levels and ER stress. Results Constitutive System x c - deficiency led to an approximately threefold decrease in glutathione levels in the pancreatic islets as well as cystine shortage characterised by upregulation of Chac1. This shortage further manifested as downregulation of beta cell identity genes and a tonic increase in endoplasmic reticulum stress markers, which resulted in diminished insulin secretion both in vitro and in vivo. Myeloid-specific deletion did not have a significant impact on metabolism or islet function. Conclusions/interpretation These findings suggest that System x c - is required for glutathione maintenance and insulin production in beta cells and that the system is dispensable for islet macrophage function.
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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